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The application of prostate-specific antigen (PSA) in the screening and diagnosis of prostate cancer (PCa) has improved the clinical management of PCa patients.However,the PSA assay has been faced with criticism due to its potential association with over-diagnosis and subsequent overtreatment of indolent patients.Matrix metalloproteinase-26 (MMP26) is a member of matrix metalloproteinases (MMPs) and has been reported to be highly expressed in many cancers.This investigation evaluated the potential of serum MMP26 as a biomarker for PCa.The level of serum MMP26 was measured by enzyme-linked immunosorbent assay (ELISA) in 160 subjects including PCa group (n=80),benign prostatic hyperplasia (BPH) group (n=40) and control group (n=40).Furthermore,we evaluated the expression of MMP26 in tissues by immunohistochemistry.The results showed the serum MMP26 levels were significantly higher in PCa group than in BPH group and control group.Similarly,the MMP26 protein was positive in PCa tissues and negative in BPH tissues and control tissues.In conclusion,these results suggested MMP26 could be used as a potential serum biomarker in the diagnosis of PCa.
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OBJECTIVE To observe the anti-aging effects of SOD mimicAEOL-10150 in anti-senescence accelerated mouse resistant 1 (SAMR1) strain. METHODS The lifespan of SAMR1 mice were observed by subcutaneous injection AEOL-101502 mg·kg- 1 once a week. Morris water maze, new object recognition, nesting and forced swimming were used to observe the behavioral changes of animals. Lymphocyte subgroups and ROS were measured by Flow cytometry. The cytokines levels were determined by Luminex method. The number of DCX + neurons in brain tissue was observed by immunofluorescence. RESULTS The results showed that AEOL-10150 could prolong the mean lifespan of SAMR1 mice, but it had no obvious effect on maximal lifespan. What's more, AEOL-10150 could significantly improve the spatial learning memory of aged mice, but it could not increase the number of DCX+ neurons in the hypothalamic MBH and hippocampal DG regions. Then, we observed the effects of AEOL-10150 on peripheral blood lymphocyte subgroups and cytokines. We found that AEOL-10150 significantly modulated the lymphocyte subgroups and cytokine release. Especially, AEOL-10150 can dose-dependently inhibit plasma levels of SASP related inflammatory cytokines TNF-α and IL-17. CONCLUSION The results indicate that AEOL-10150 has anti-aging effects, and the effects are closely related to modulating immunity and inhibiting SASP production.
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In this study,the current status for breast diseases in a region with high-incidence of cervical cancer were epidemiologically investigated.From March to August,2009,17618 women,from Wufeng area of Hubei province,China,were recruited to screen breast diseases by using breast infrared diagnostic apparatus.Other diagnostic methods,such as B-mode ultrasound,X-ray mammography,needle biopsy and pathological examination were,if necessary,used to further confirm the diagnosis.The screening showed that 5990 of 17618 cases (34.00％) had breast diseases,5843 (33.16％) had mammary gland hyperplasia,48 (0.27％) had breast fibroadenoma,ll (0.06％) had breast carcinoma,and 88 (0.50％) had other breast diseases.The peak morbidity of breast cancer was found in the women aged 50-0 ages.The morbidity of breast cancer was significantly increased in women elder than or equal to 50 years old (n=8,0.157％) in comparison with that in the subjects younger than 50 years old (n=3,0.024％) (u=2.327,P＜0.05).It was shown that the occurrence of breast diseases was concentrated in women aged 20-40 years,while the total morbidity reached its peak at the age of 30 years and then decreased sharply after age of 40.Compared with the patients elder than or equal to 40 years old (n=3289,27.46％),the morbidity rate of breast diseases was significantly increased in women less than 40 years old (2648 cases,47.18％; P＜0.001).However,there was no significant difference in the morbidity of breast diseases between the age group of 20-29 years and that of 30-39 years (P=0.453),and both of them were high.There was no significant association between the morbidity of breast diseases and cervical cancer.Since the morbidity of breast diseases was higher among young women,more attention should be paid to the screening of breast diseases among young women for early diagnosis.
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The purpose of this study was to pool information in epithelial ovarian cancer by combining studies using Affymetrix expression microarray datasets made at different laboratories to identify novel biomarkers.Epithelial microarray expression information across laboratories was screened and combinedafter preprocessing raw microarray data,then ANOVA and unpaired T test statistical analysis was performed for identifying differentially expressed genes(DEGs),followed by clustering and pathway analysis for these DEGs.In this work,we performed a combination analysis on microarrays from three different laboratories using gene expression data on ovarian cancer and obtained a list of differential expression profiles identified as potential candidate in aggressiveness of ovarian cancer.The clustering and pathway analysis explored the different molecular basis of different ovarian cancer stages and potential important regulatory pathways in ovarian cancer development.Our results showed that combination of microarray data from different laboratories in the same platforms may overcome biases derived from probe design and technical features,thereby accelerating the identification of trustworthy DEGs,and demonstrating the advantage of integrative analysis in gene expression studies on epithelial ovarian cancer research.
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The mRNA and protein expression of thymidylate synthase(TS),thymidine phosphorylase(TP)and dihydropyrimidine dehydrogenase(DPD)and their relationship with prognosis were investigated.Real-time quantitative RT-PCR(Taqman)was used to detect the mRNA expression of TS,TP and DPD in formalin-fixed and paraffin-embedded 106 samples of epithelial ovarian cancer and 29 normal ovaries.A TATA box-binding protein(TBP)was used as an endogenous reference gene.A relationship between TS,TE DPD expression and clinicopathologic features was investigated.The protein location and expression of TS,TP and DPD was examined in the same patients by an avidin-biotin-peroxidase immunohistochemistry.TS and TP mRNA expression levels were significantly higher in tumor group than in normal controls,with the average value of TS and TP mRNA being 6.14±0.62 and 0.59±0.06 in tumor tissue,and 0.71±0.14 and 0.16±0.04 in normal tissue,respectively.DPD mRNA expression levels were significantly lower in tumor group(0.11±0.02)than in normal controls(0.38±0.05).There was statistically significant difference in TS and TP mRNA expression levels among different pathological grades and clinical stages(P<0.05),but histological subtype was not significantly associated with TS and TP mRNA expression.DPD gene expression was not significantly associated with any clinicopathological parameters.Immunohistochemistry revealed that TP protein was mainly distributed in nucleus,and TS and DPD mainly in cytoplasm.The protein expression intensity of TS,TP and DPD was coincided with the mRNA expression levels.It was concluded that TS,TP mRNA and protein expression levels were significantly higher in epithelial ovarian cancer,and DPD mRNA and protein expression levels were significantly lower.The expression levels of TS and DPD were related to the patients' prognosis and survival.Combined gene expression levels of TS,TP and DPD represent a new variable to predict the clinical outcome in ovarian cancer.The association of TS,TP and DPD expression levels with survival suggests an importance of these genes for tumor occurrence and progression.
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In this article, the status of spindle assembly checkpoint and the alteration of its major component, Mad2 protein level were examined in A2780 and SKOV3 ovarian cancer cell lines. Recombinant eukaryotic expression plasmid pEGFP-Mad2 was transfected into paclitaxel-resistant SKOV3 cells and Mad2 protein was knocked down by Mad2-specific siRNA in paclitaxel-sensitive A2780 cells. Then the expression level of Mad2 gene was detected by Western blotting. Flow cytometry revealed that SKOV3 cells were not fully arrested in G2/M phase in contrast to A2780 cells in the presence of paclitaxel. However, paclitaxel sensitivity assay showed that sensitivity to paclitaxel was reversed after the transfection in both cell lines in terms of number of cells arrested at G2/M phase and the expression of Bcl-2 was significantly changed. These results suggest that weakened spindle checkpoint with reduced expression of Mad2 is associated with resistance to paclitaxel in ovarian cells and Bcl-2 may be involved in this process.
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Small cell carcinoma of cervix (SCCC) is a rare disease with highly aggressive behaviour and is pathologically hard to diagnose. In this study, the clinicopathological features, diagnosis,treatment and prognosis of the condition were examined. Clinical records and follow-up data of 7 cases of SCCC were retrospectively studied. Our results showed that five non-recurrent cases initially presented irregular vaginal bleeding or increased apocenosis of varying degrees. Pathological examination revealed that the stroma was diffusely infiltrated with small monomorphous cells ranging from round to oval shape. Three cases were immunohistochemically confirmed. One case was accompanied with squamous cell cancer. Of the 7 cases, one case was classified as stage Ⅰ bl, two stage Ⅰ b2,one stage Ⅱ a, one stage Ⅱ b, and one stage Ⅲb. On the basis of their stages of condition, one subject with stage Ⅲ b underwent chemotherapy, and one with stage Ib2 received extensive hysterectomy plus pelvic lymphadenectomy, while the other 5 cases were treated by extensive hysterectomy and pelvic lymphadenectomy in combination with pre- and/or post-operative adjuvant chemotherapy and radiotherapy. Of the 7 patients, 4 had relapse-free survival of 14, 14, 16 and 28 months respectively.It is concluded that SCCC is an aggressive tumor with propensity for early pelvis lymph node metastases. Early-stage patients should be treated by extensive hysterectomy and pelvic lymphadenectomy in combination with pre- and/or post-operative adjuvant chemotherapy and radiotherapy.
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Recent evidence has suggested that Akt2 plays an important role in the protection of cells from paclitaxel(PTX)-induced apoptosis and control of the cell cycle.In addition,some scholars suggested that the PTX sensitivity depends on a functional spindle assembly checkpoint.In the present study,we investigated the role of the Akt2/Bub1 cross-talking in apoptosis and cell cycle after exposure of the A2780 ovarian cancer cells to paclitaxel(PTX).Recombinant expression plasmid WT-Akt2 was transfected into A2780 cells by lipofectamine2000,and then the expression level of Akt2 gene was detected by using RT-PCR and Western blotting.Cell apoptosis and cell cycle were detected by flow cytometry and Hoechst 33342 staining after treatment with PTX.Moreover,we compared the expression level of Bubl in different groups by Western blotting.Our study showed that up-regulation of Akt2 contributed to A2780 ovarian cancer cells overriding PTX-induced G2/M arrest,and inhibited Bub1 expression.Our findings might shed light on the molecular mechanism of PTX-induced resistance in ovarian cancer and help develop novel anti-neoplastic strategies.
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In order to investigate the role of the PTEN expression in carcinogenesis and develop-ment of endometrial carcinoma and clarify whether and how PTEN and PI3K/Akt pathway relate to endometrial carcinoma,the expression of PTEN and phospho-Akt was detected by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) methods and Western-blot from 24 cases of endomctrial carcinoma,10 cases of endometrial atypical hyperplasia,10 cases of endometrial hy-perplasia,and 10 cases of normal endometrium.SP immunohistochemical methods were used to measure levels of PTEN protein expression in following 5 study groups:31 cases of endometrium in proliferative phase,30 cases of endometrium in secretory phase,71 cases of endometrial hyperplasia,25 cases of atypical hyperplasia and 73 cases of endometrial carcinoma.Immunostaining score of PTEN was 3.39±0.15 in proliferative phase,1.90±0.21 in secretory phase,3.34～0.29 in endometrial hyperplasia,0.624±0.11 in atypical hyperplasia,and 0.74±0.19 in endometrial carcinoma,respectively.PTEN mRNA relative value in normal endometrium,endometrial hyperplasia,endometrial atypical hyperplasia,and endometrial carcinoma was 2.45±0.51,2.32±0.32,0.46±0.11,and 0.35±0.13 respec-tively.The expression levels of PTEN mRNA and protein in patients with endometrial carcinoma and atypical hyperplasia were significantly lower than in those of proliferative phase and with endo-metrial hyperplasia.The level of PTEN expression in patients with endometrial carcinoma was sig-nificantly related to tissue type (P<0.005),differentiation (P<0.05) and clinical stage (P<0.05),but not to depth of myometrium invasion (P>0.05).Western blot analysis revealed that Phospho-Akt level in PTEN negative cases was significantly higher,and there was a negative correlation between PTEN and phospho-Akt (r=- 0.8973,P<0.0001).It was suggested that loss of PTEN expression was an early event in endometrial tumorigenesis.The phosphorylation of Akt induced by the loss of PTEN took part in the tumorigenesis and development of endometrial carcinoma.
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Summary: Glomerulosclerosis, defined as phenotype transition of mesangial cell and deposition of extracelluar matrix, remains a chronic disease with excessive morbidity and mortality. The molecular mechanism underlying the suppression of mesangial cell activation is not fully understood. Since activation of peroxisome proliferators-activated receptor γ (PPAR1,) has been proposed to decrease the effects of transforming growth factor-β (TGF-β) on glomerulosclerosis, we examined here whether and how telmisartan, an angiotensin Ⅱ type Ⅰ receptor blocker with PPARγ-modulating activity, inhibited TGF-β-induced giomerulosclerosis in rat glomerular mesangial cells. Protein levels of PPARγ were detected by Western blot. Activation of PPARγ response element (PPRE) was analyzed by luciferase assays. Deposition of extracelluar matrix was tested by confocol laser scanning. The results showed that telmisartan, but not valsartan, another angiotensin Ⅱ type Ⅰ receptor blocker,up-regulated PPARγ protein levels in a dose-dependent manner (P<0.05). Activation of PPRE, represented by luciferase activity, was also increased with higher concentration of telmisartan in a dose-dependent manner (P<0.05). Furthermore, telmisartan inhibited TGF-β-induced α-smooth muscle actin expression and collagen IV secretion in mesangial cells. GW9662, an inhibitor of PPAR-γ,blocked the inhibitory effects of telmisartan on TGF-β-induced glomerulosclerosis in mesangial cells. Our study indicates a benefit of telmisartan as a PPARγ agonist against TGF-β-induced mesangial cells activation in renal glomerulus. It may provide possibility that telmisartan works as a potential agent against diabetic nephropathy and hypertensive renal disease.
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To screen for novel binding proteins interacting with high-risk HPV 18 E6 oncogene, the strain AH109 was transformed with pGBKT7-HPV18 E6 plasmid, and subsequent transference was utilized to screen for interacting proteins with HPV 18 E6 in human Hela cDNA library. HPVl8 E6 mRNA was expressed in yeast and there was no self-activation and toxicity in AH109. Seven proteins that interacted with HPV18 E6, including transmembrane protein 87B, phosphonoformate im- muno-associated protein 5, vimentin, KM-HN-1 protein, dedicator of cytokinesis 7, vaccinia related kinase 2 and a hypothetical protein, were identified. It was suggested that yeast two-hybrid system is an efficient for screening interacting proteins. The high-risk HPV 18 E6 oncogene may interact with the proteins, which may be associated with signal transduction and transeriptional control, epithelial cell invasion and migration, as well as humoral and cellular immune etc. This investigation provides functional clues for further exploration of potential oncogenesis targets for cancer biotherapy.
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To study the apoptosis induced by cisplatin in cervical cancer cell line HeLa and its mechanism, cell growth inhibition of cisplatin on HeLa cells was analyzed by MTT assay. Cell apoptosis was examined by cytometry and Hoechst33258 staining after treatment with cisplatin. The ef- fects of cisplatin on transcription of E6 were analyzed by RT-PCR. The protein expressions of E6, p53, p21, Bax and Bcl-2 were studied by Western blotting. Cisplatin inhibited proliferation in a time- and dose-dependant manner. Cytometically, sub-G1 peak showed higher apoptosis rates in the ex- perimental group than those in the control. Hoechst33258staining exhibited apoptosis induced by cis- platin. RT-PCR revealed that cisplatin decreased transcription of E6. Western blotting showed that cisplatin decreased protein expression of E6 and increased protein expression of p53, p21and Bax. It had no effect on protein expression of Bcl-2. It is concluded that cisplatin can induce apoptosis in HeLa cells by suppressing HPV E6 and thereby restoring the function of p53.